Development and Evaluation of Donepezil loaded PEGylated Dendrimers for the treatment of Alzheimers Disease

Abstract

Development and Evaluation of Donepezil loaded PEGylated Dendrimers for the treatment of newlineAlzheimer s Disease newlineAbstract newlineAim and objectives: Now days, it is major challenge for researchers and physicians to achieve maximum concentration of the therapeutic in CNS targeting for management of Alzheimer s disease, with greatest bioavailability. Thus, there is an indeed need of stable, biocompatible, potent drug delivery system which can offer maximum bioavailability of therapeutic agents for management of Alzheimer s disease. The present study was aimed to develop donepezil loaded PEGylated Polypropylenimine dendrimers administered through olfactory route for improving bioavailability of donepezil HCl in brain. newlineMaterial and methods: The PPI dendrimers were synthesized by divergent method and characterized by IR, NMR and microscopically. The synthesized dendrimers were PEGylated with MPEG 5000 and were characterized by IR, NMR and microscopically. The PEGylated dendrimers were evaluated for their biocompatibility and safety with acute toxicity studies on Wistar albino rats, including haematological, biochemical, histopathological parameters. PEGylated 3.0G, 4.0G and 5.0 G were evaluated for their entrapment efficiency of donepezil HCl. The donepezil loaded PPI dendrimers were characterized by IR, NMR and TEM microscopy and then evaluated for In-vitro release studies, stability, drug leakage, storage and haemolytic activity. Ex-vivo study was performed on goat nasal mucosa to check nasal diffusion capacity of the developed formulation followed by nasal histopathology to check the bio-safety of developed formulation on nasal mucosa. In-vivo pharmacokinetic and Pharmacodynamicstudies were carried out using Wistar Albino rats.. Pharmacokinetic estimation included study of bioavailability, Cmax, Tmax, T1/2, AUC and MRT. Pharmacodynamic studies included testing of neurobehavioural parameters of animals on Y- maze and fear conditioning. newlineResults: The synthesis of different generations of PPI dendrimers was confirmed by